The object of the proposed research is to study the mechanisms of ionic transfer across the epithelial cell layer of the respiratory tract. Isolated lung tissue will be used as an experimental system, and a wide spectrum of analytical and electrophysiological techniques will be brought to bear on the problem under investigation. These include: the measurement of transepithelial potential difference, short circuit current, and epithelial cell membrane potentials; determination (by atomic absorption spectrophotometry) of intracellular sodium and potassium concentrations; measurement (by electrometric titration) of intracellular chloride concentrations; determination, with ion-selective microelectrodes, of intracellular sodium, potassium, and chloride activities and measurement, using radiotracer techniques, of transepithelial and transmembrane ionic fluxes. Since active ion transport is known to occur in airway epithelim, and since, in virtually every epithelial preparation which has been systematically studied, water flow has been found to be linked to ionic transfer processes, the characterization of ion flows in the respiratory tract which this investigation seeks to accomplish should serve to help define the forces involved in the secretion of fluid into the airway lumen. It is probable that such secretion plays an important role in mucociliary clearance and defects in fluid secretion may be important in such pathological conditions as cystic fibrosis, status asthmaticus and chronic bronchitis. Animal models for some of these conditions (e.g. chronic bronchitis) have been developed and will be utilized in this study. A novel aspect of the proposed investigation is the application of techniques for measuring intracellular ionic activities to isolated airway epithelium.